Clinical Trials Office
Gemma Sala
Director
Summary
Launched in 1997, our Clinical Trials Office incorporates experts conducting clinical trials at the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department, the Vall d’Hebron Barcelona Hospital Campus. Headed by VHIO’s Director, Josep Tabernero, our team comprises study coordinators, data managers, sample managers, administrative as well as quality control staff, who coordinate phase I–IV clinical studies and also participate in several translational research projects at VHIO.
Organized into three groups, covering all tumor types and studies, our personnel are managed by the Clinical Trials Office Director, Gemma Sala.
In 2019 we managed 1 phase 0, 139 Phase I, 23 Basket studies, 141 phase II, and 121 phase III clinical trials with active recruitment throughout the year (see Figure), with patient enrolment totaling at 1122. 150 new trials were initiated, including 8 post-authorization trials and rollover studies. In addition, we continue to follow up patients who were recruited prior to 2019 and are still enrolled and receiving study treatment (more than 900 patients in total, and more than 1400 in follow up).
More than half of our patients included in our Phase I Clinical Trials have been referred to us from other Hospitals, which has consequently positioned our Unit as leading reference in early clinical studies.
As a reflection of our continued expansion as well as recognition of excellence, we have undergone 16 audits with positive results and VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) –”la Caixa”, directed by Elena Garralda, has been reaccredited by the Generalitat de Catalunya.
As we continue to render personalized medicine more precise by matching therapies to respond to the specificities of each individual patient, each individual tumor, the requirements and selection criteria for inclusion in certain studies are also becoming more complex.
While we are dedicated to expanding our portfolio of trials in order to ultimately establish new treatment models with highly selective drugs, we continue to fine-tune patient selection criteria in order to best identify those patients who are most likely to benefit from novel therapies, including emerging immune-based therapies, tailored to individual patients’ molecular ‘measurements’.
The prestige of our Hospital’s Medical Oncology Department is increasingly recognized by pharmaceutical as well as biotechnology companies. It has also become a reference program and selected by the industry to carry out complex clinical trials for which the number of participating centers is highly restricted.
Clinical sites are selected based on the highest standards of quality and capacity for carrying out state-of-the-art research. We have participated in early phase trials of different drugs, ultimately enabling the pharmaceutical industry to market novel anti-cancer medicines. We are involved in studies promoted by the pharmaceutical industry as well as those developed by us in collaboration with other hospitals. We have also conducted more than 10 Investigator-Initiated Trials (IITs).
Annual recruitment of patients enrolled in Clinical Trials (Phases 0, I + Baskets - II–III)
Annual Distribution of Phases 0, I + Basket, II and III Trials
Strategic goals
- Contribute to the development of novel therapies against cancer.
- Consolidation as an international reference for clinical trials in oncology.
- Guide patients enrolled in trials to comply with the protocol requirements and help them with daily life throughout the duration of their participation. Ensure that protocols are managed and followed from initiation to the close of the respective clinical study.
- Standardize clinical trial processes to ensure optimal quality and the compliance of Good Clinical Practice (GCP).
Highlights
- Our Clinical Research Support Unit, which was set up in 2016, continues to guide investigators with the start-up and management of independent research lines.
- We continue to report important numbers of clinical trials performed and respective patient recruitment.
- Optimal management of the complexity of protocols which are increasingly demanding.
- We have provided tailored training for our staff in order to further improve the quality of our work and expand related skill sets.
- Implemented new tools and procedures aimed at increasing the quality and efficacy of research.
- Continued optimal quality and procedures achieved through the Inspection for Accreditation of our phase I Unit, the Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, by the Generalitat de Catalunya, carried out in 2016. We received reaccreditation in 2019.
- New patient monitoring system employing electronic medical records.
- Increased office space for the management and coordination of our activities.
Horizons
- Over the last few years our Clinical Trials Office has not only improved quantitatively but also qualitatively. Our main objective for the future is to continue expanding our portfolio of clinical studies, maintain the high quality offered in-house as well as to our patients, and thus continue to be a reference for novel cancer therapies and precision medicine in oncology.
- We plan to both consolidate and expand our Clinical Research Support Unit that we launched in 2016.
- We aim to update and create new SOPs to ensure the standardization and quality of all procedures performed in clinical trials.
- Create new tools and systems to standardize and facilitate procedures for our studies.
- Focus on managing Investigator Initiated Trials (IITs).
- Continue with our GCP course.
- Training programs for out team members.
- Optimal data completion and exploitation using the software for clinical trial management.
- Renewal of accreditation.
- Continue to integrate VHIO’s Experimental Hematology Group study coordinators within our team to align processes and Standard Operating Procedures (SOPs).
Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”
Josep Tabernero
Director of Clinical Research
Summary
Inaugurated in June 2010, thanks to the support received from the ”la Caixa” Foundation, the Research Unit for Molecular Therapy of Cancer (UITM) –”la Caixa”, is dedicated to complex clinical trials with drugs in early development (phase I and early phase II trials), focusing on novel targets. Occupying a total surface area of 1000 m2 our Unit is located within the General Area of the Vall d’Hebron University Hospital (HUVH), the Vall d’Hebron Barcelona Hospital Campus.
This privileged environment with direct access to patients, coupled with VHIO’s translational approach to research and superb scientific framework, has enabled our Unit to rapidly establish itself as one of the few comprehensive facilities in Europe to rapidly transform latest discovery into benefits
for patients.
By promoting tight connectivity between oncology care and research we establish novel treatment models for patients with highly selective drugs, and advance insights into tumor diseases and how to treat them in an individualized way – getting the right therapy to the right patient at the right time. As the figures show, we are gradually doing so for an increasing number of patients.
In 2019, also thanks to the support received from the ”la Caixa” Foundation, the building of VHIO’s Clinical Research Oncology Pharmacy’s Unit’s (led by Maria Queralt), new Facility, the Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”- Clinical Research Onco-Hematology Unit was completed. Equipped with all with all the very latest technologies, this will enable them to provide even higher quality pharmaceutical care and continue to respond to all regulatory requirements.
This year, our Unit has participated in 162 ongoing phase I clinical trials, 23 of which are Basket trials. Our facilities, coupled with our multidisciplinary clinical teams, enable us to continue to expand our portfolio of phase I studies. This year we opened 46 new trials; 6 as Baskets. 499 patients were recruited, 241 of whom were enrolled in immunotherapy clinical trials.
Research carried out at our Unit by VHIO’s Early Clinical Drug Development Group directed by Elena Garralda, centers on the development of new drugs based on the molecular profile of each tumor as well as the optimization of treatment regimens using combinations of new agents with those that already exist.
Reflective of VHIO’s purely translational model, our studies are also linked to several research lines led by other VHIO groups, thus connecting molecular biology and optimal tumor models with pharmacology and innovative clinical research. VHIO scientists also collaborate closely in our trials to facilitate biomarker development, a deep understanding of the mechanism of action, as well as research into mechanisms of cancer drug resistance.
In partnership with VHIO’s Cancer Genomics (PI Ana Vivancos), Molecular Oncology (PI Paolo Nuciforo), and Oncology Data Science - ODysSey (PI Rodrigo Dienstmann), together with Susana Aguilar and Jenifer Gonzalez, we perform molecular analyses of patients’ tumors to select the best possible treatment with the experimental therapeutics available. Thanks to our Cancer Genomics Group’s development of existing applications for faster results including an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina) we continue to drive faster and more precise mutational analyses of tumor suppressor genes as well as translocations and gene amplifications.
UITM incorporates a multidisciplinary team comprised of medical oncologists, clinical trial coordinators and data managers, nurses and nurse technicians, pharmacists, as well as administrative personnel.
Excellent patient treatment and care as well as pioneering research is also made possible thanks to the collaboration of many other oncology professionals including our team of Clinical Research Oncology Nurses led by Mª Angeles Peñuelas, pathologists from the Vall d’Hebron University Hospital’s Molecular Pathology Department, radiologists and interventional radiologists, as well as our Clinical Trials Office and Database Management, directed by Gemma Sala, Clinical Research Oncology Pharmacy Unit headed by Maria Queralt, and other healthcare specialists including dermatologists, cardiologists, and ophthalmologists.
Strategic goals
- Early drug development and translational research led by UITM physician-researchers and VHIO scientists: expansion of our broad portfolio of promising novel anticancer therapies, across a balanced spectrum of studies, with special focus on first-in-human studies, novel-novel combinations, best-in-class compounds, and a new class of drugs.
- Perform complex trials such as organ dysfunction trials, Octopus as well as Basket studies, and link clinical research at UITM to VHIO's preclinical and translational projects. Our Unit also collaborates with the various partners involved in drug development and translational research.
- Genomic medicine trials in early drug development: perform molecular analysis of patients' tumors in order to select the best possible treatment with the experimental treatments available, co-develop medical informatics applied to genomic medicine, and integrate preclinical and clinical research by incorporating novel drugs, new insights, and study design together with customized molecular diagnostics.
- Immunotherapy: our Unit's taskforce in early drug development of immunotherapeutics and cell signaling focuses on second generation immunotherapies, including new cytokines, bispecifics, intratumoral agents, immunomodulatory, and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology.
Highlights
- We have performed some of the most complex phase I trials, including those focused on molecularly-selected patient populations (trials in complex molecularly-selected patient populations Basket/Octopus trials) as well as trials in immuno-oncology.
- We have expanded our expertise in drugs targeting developmental pathways, cell signaling (ERK, MET, FGFR, RET, NOTCH, NTRK), and immunotherapy (LAG3, TIGIT, OX40, CD40, IDO, arginase inhibitors and engineered antibodies).
- Developed by VHIO's Cancer Genomics Group, PI: Ana Vivancos, we benefit from applications for faster results including an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina). We also co-develop customized molecular tests for VHIO's Prescreening Program (disease-oriented mutation panels for our NGS platforms).
- We have developed alliances with many pharma companies as the preferred site for testing their novel and most relevant therapies, including GlaxoSmithKline OCTC, Roche ImCORE, and AstraZeneca/MedImmune, Partners of Choice.
- We have successfully implemented the Basket of Baskets (BoB) trial which is a novel study in personalized medicine integrating cutting-edge molecular prescreening, the development of new diagnostic tests such as circulating DNA or Nanostring, with the testing of targeted therapies in populations of patients with identified molecular alterations in their tumors and a high probability of benefiting from the selected treatments. This is an academic study, endorsed by the Cancer Core Europe (CCE) consortium, and co-funded by pharmaceutical companies. The first module evaluating atezolizumab in a molecularly-selected population recruited this year, and we have secured funding to evaluate FGFR inhibition in specific populations. We are engaged in ongoing and advanced negotiations with other pharmaceutical companies.
- We have introduced Molecular Tumor Board meetings to discuss the most relevant genomic features of complicated cases to evaluate possible treatment options.
- We have started an advanced cell-based therapy program, and are participating in several pharma sponsored trials to evaluate the role of TIL therapy as well as exploring an academic TIL product in collaboration with Alena Gros, PI of VHIO’s Tumor Immunology & Immunotherapy Group.
- In collaboration with several other VHIO groups, we head the VHIO-"la Caixa" Advanced Oncology Research Program (2020-2023).
Horizons
- Expand our number of clinical trials adding new targeted therapies against novel promising targeted therapies and best-in-class therapies.
- Reinforce our translational research efforts to deepen our knowledge of cancer progression and treatment mechanism of resistance.
- To continue our participation in the field of precision cancer medicine. We will continue to raise funds for the Basket of Baskets project. Increase our portfolio of molecular tests, adding new panels and tests to our program such as gene expression signatures and liquid biopsies- Converge immuno-oncology, genomics, and other predictive biomarkers to further enhance and expand precision medicine against cancer with immune therapies.
- To increase our expertise in the Immuno-oncology area and develop expertise in the emerging field of Epigenetics and on the signaling between tumor cells and the immune system.
- To expand our program for advanced therapies in solid tumors. Implement our own academic TILs program in collaboration with Alena Gros, CAR-T, NK cells (in collaboration with the Clínica Universitaria de Navarra), and other cell therapies. To become a referral unit of these therapies also for pharma sponsored trials.
- To include artificial intelligence and big data, and digitalize our Phase I Unit. Participate in initiatives to develop clinical support systems, such as the MTB portal in CCE.
- To increase the number of academic trials led by our Unit.
Clinical Research Oncology Nurses
Mª Angeles Peñuelas
Nurse Supervisor
Summary
Clinical trials in oncology are essential for the identification of novel, more effective targeted therapies against cancer as well as improving survival, side effect profiles and the quality of life of patients. Advances in oncology care and the development of more powerful anti-cancer medicines are driven by optimal processes in clinical trials.
Our expert clinical research oncology nurses assume a central role by undertaking a variety of roles including identifying trends in side effects, closely collaborating with multidisciplinary teams to develop and evaluate patient management, contributing to clinical studies by collating samples and quality data, as well as providing excellence in nursing care and symptom management for all patients enrolled in clinical trials.
VHIO's Clinical Research Oncology Nurses, specialized in molecular therapies, are headed by Angeles Peñuelas and represent an important element of the multidisciplinary teams involved in the studies performed and coordinated at VHIO's Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa” and Clinical Trials Office, directed by Elena Garralda and Gemma Sala, respectively.
Supporting these teams comprised of medical oncologists, molecular pathologists, oncology pharmacists, clinical researchers, and study coordinators, VHIO's oncology nurses are key to ensuring the delivery of optimal care for patients who receive the full range of expertise, guidance, and the necessary follow-up throughout the course of their participation in a clinical study.
As importantly is the psychological support they provide, alongside the other superbly trained oncology care givers and specialists including psychologists. Our nurses also provide patients and their families with the information and professional guidance they need to make fully informed decisions concerning their treatment options.
In 2019, across the 425 actively recruiting trials patient enrollment totaled at 1122. Our clinical teams also continue to follow up patients that were recruited prior to 2019 who are still enrolled and receiving treatment.
As VHIO continues to expand its portfolio of clinical trials to ultimately establish novel treatments with highly selective drugs, and fine-tune patient selection criteria in order to identify those patients who are most likely to benefit from them, we can expect a steady increase in patient recruitment across our clinical studies in the future.
Clinical Research Oncology Pharmacy Unit
Maria Queralt Gorgas
Clinical Director of the Clinical Research Oncology Pharmacy Unit
Summary
Our Unit is ISO 9001:2015 certified and affiliated with the Medical Oncology Service of the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus. As noted in our Highlights section above, thanks to the support received from the ”la Caixa” Foundation, the building of our new Facility, the Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”- Clinical Research Onco-Hematology Unit was completed. Equipped with all with all the very latest technologies, this will enable us to provide even higher quality pharmaceutical care and continue to respond to all regulatory requirements.
We focus on two main areas of clinical research in oncology:
Oncology Pharmaceutical Care Program
Our team of pharmacists specialized in hospital pharmacy and oncology pharmacy and our laboratory technicians prepare cytostatics and other parenteral therapies used in clinical trials. They also monitor and follow-up patients.
Pharmacological Research in Oncology Support Program
This program is led by our team of pharmacists and laboratory technicians specialized in clinical trials, who are responsible for study supplies management, storage, dispensation, and traceability control.
In 2019 we managed drugs used in 591 active clinical trials in oncology & hematology, and 7.426 resupply deliveries/clinical trials supplies receptions. We continue to benefit from our cutting-edge system for controlling storage temperature which, performing electronic temperature recordings every 5 minutes daily, displays readings on computers equipped with audiovisual alarms as well as an around-the-clock SMS alert system to monitor and report temperature deviations.
Regarding the design and validation of our drug preparation process traceability system, we ensure qualitative and quantitative quality control of our computerized system.
In 2019 our dispensing staff actively participated in 113 pre-study visits, 185 initial visits, 1,841 monitoring visits, 111 close-out visits. We have also successfully passed 21 audits, 1 mock inspection, 1 ISO inspection, and 1 inspection by local regulatory authorities for reaccreditation of our Oncology Phase I Unit.
Additionally, 39,055 clinical trial drugs have been dispensed and validated by our pharmacists, 13,782 of which were for oral administration, 1,017 for IM/ subcutaneous administration, and 24,256 for IV administration. A total of 214 Standardized Dispensing Procedures for clinical trials have been drawn up and we have performed 892 updates of these procedures due to subsequent amendments to protocols or pharmacy manuals. 156 storage temperature data reports have also been prepared by our dispensing team.
Preparations of cytostatics, monoclonal antibodies and other parenteral antitumor drugs for clinical trials totaled at 24,122. We also included 432 antineoplastic therapeutic schedules in our prescription software.
Our Pharmaceutical Care Program for patients enrolled in phase I clinical trials: we performed 1,205 visits, 253 screenings, 238 C1D1s, and 221 follow-ups, also compiling patient diaries and/or instructions for patients (in the absence of documentation provided by the respective sponsor).
We have also compiled 15 different diaries and 15 instruction manuals for patients enrolled in the phase I studies involving orally administered drugs by our preparation staff. We also prepared 23 diaries and patient manuals for phase II and phase III clinical trials in 2019 for patients enrolled in all phase II and III studies involving orally administered drugs by our dispensing staff.
Strategic goals
- Excellence in the services we provide to clinical oncology research programs through optimal efficacy, efficiency and safety.
- Management, dispensing, preparation and administration of clinical study drugs according to protocol specifications. Ensure traceability of the entire circuit with the development and implementation of new software.
- Maximized control of storage temperature of samples and preparations.
- Optimal use of a computerized program, IPharma-FUNDANET®, for the management of clinical trial supplies.
- Provision of a pharmaceutical care program for patients in phase I studies treated with orally administered medicines to improve safety, compliance and efficacy of these therapies.
- Provide instructions and indications to patients for orally administered therapies in phase II and III studies.
- Successful sponsor audits as well as inspections carried out by regulatory authorities.
Highlights
- In 2019, thanks to the support received from the ”la Caixa” Foundation, the building of our new facility, the Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”- Clinical Research Onco-Hematology Unit was completed. Equipped with all with all the very latest technologies, this will enable us to provide even higher quality pharmaceutical care and continue to respond to all regulatory requirements.
- Replacing paper medical orders, we have implemented electronic prescription ordering for IV administration medication in our site prescription software.
- We have developed new traceability software that includes global pharmacotherapeutic processes; the prescription, validation, dispensing, preparation and administration of drugs in the oncology and hematology clinical trial setting.
- Our Unit has provided clinical and technical support for the prescription, preparation, and administration of cytostatics in clinical trials, providing e-records of usage and timings.
- Qualitative and quantitative quality control of all parenteral anticancer preparations to guarantee patient safety and protocol compliance.
- ISO9001:2015 certification renewed. Successful sponsor audits, regulatory inspections, and participation in the renewal of VHIO’s Phase I Unit reaccreditation.
Horizons
- Excellence in the quality of services we provide for various clinical research programs and clinical trial sponsors.
- Continue to ensure optimal quality of the pharmaceutical care services that we provide to all patients enrolled in Phase I clinical trials.
- Maintain excellence in the quality of services that we provide -in both pharmaceutical care and dispensing- to our patients receiving oral drugs.
- Expansion of our new traceability software that includes the global phamacotherapeutic processes involved in the oncology and hematology clinical trials’ setting.
- Optimal temperature control and conditions for the storage of clinical trial supplies.
- Continue to receive good results from audits and regulatory (BOH, EMA or FDA) inspections.
- Successful annual renewal of ISO 9001/2015 certification.